Patent GB-1264941-A (GB)
IPC: C07J41/00
Filed: 1970-03-19
Abstract: 1,264,941. 2-Androstene 17-ethers. MERCK PATENT G.m.b.H. 19 March, 1970 [12 April, 1969], No. 13298/70. Heading C2U. Novel steroids of'the formula (wherein R<SP>1</SP> and R<SP>2</SP> are each C 1-3  alkyl, or -NR<SP>1</SP>R<SP>2</SP> is pyrrolidino, piperidino, hexamethyleneimino, 1-piperazinyl or morpholino, and n is 2, 3 or 4) and salts thereof are prepared (a) from corresponding 17#-X-steroids and amines Y-C n H 2n -NR<SP>1</SP>R<SP>2</SP>, where X and Y are OH or functional derivatives thereof, or one of them is a halogen; or (b) by N-alkylation of corresponding 17#-OC n H 2n NHR<SP>3</SP> steroids, where R<SP>3</SP> is H or C 1-3  alkyl; or (c) by condensation of corresponding 17#-OC n H 2n Z-steroids, where Z is as X or Y with an amine NHR<SP>1</SP>R<SP>2</SP>; or (d) by reacting corresponding 3#-Z-ring A-saturated steroids with a compound capable of splitting off HZ; or (e) by reducing corresponding steroids containing a carbonyl or thiocarbonyl group in the 17-side chain adjacent to the O or N atom, or by reducing corresponding steroids containing an episulphide group in the 2,3- position or a #<SP>2</SP>-3-thioenol ether grouping. 2-Androsten-17α-ol is prepared, together with the corresponding 17#-ol, from which it is separated chromatographically, by reduction of the corresponding 17-one, and is subsequently converted to its tosylate. 17α-Bromo-2-androstene is prepared by the action of KBr on the corresponding 17#-ol tosylate. 17#-(2-aminoethoxy)-2- androstene is prepared from the corresponding 17#-ol via 17#-(2-hydroxyethoxy)-2-androstene and 17# - (2 - chlorethoxy) - 2 - androstene 17(3- (3 - aminopropoxy) - 2 - androstene is prepared by cyanoethylation of the 17#-ol followed by reduction. 17# - (4 - aminobutoxy) - 2 - androstene is prepared by reacting the Na derivative of 2-androsten-17#-ol with 4-bromobutyric acid nitrite and then reducing. 17#-(2-ethylaminoethoxy)-2-androstene is prepared by reacting the 17#-ONa compound with bromoacetaldehyde diethyl acetal and hydrolysing to form 17#- formylmethoxy - 2 - androstene, reacting with ethylamine to form the Schiff's base, and reducing this. 17#-(2-chloroethoxy)-2-androstene is prepared from the 17#-ONa compound and 1 - bromo - 2 - chloro - ethane. 17#-pyrrolidinocarbonylmethoxy-2-androstene is prepared from the 17#-ol and chloroacetic acid pyrrolidide; 17# - diethylaminocarbonylmethory - 2 - androstene is prepared similarly. 17#-(2-N-acetyl-N- ethylaminoethoxy) - 2 - androstene is prepared by acetylation of 17#-(2-ethylaminoethoxy)-2-androstene. Morpholinoacetic acid - (2 - androsten- 17#-yl)-ester is prepared from morpholinoacetic acid and 2-androsten-17#-ol. 17#-(2-diethylaminoethoxy) - androstan - 3# - ol 3 - tosylate is prepared by reacting androstane-3#,17#-diol 3-tetrahydropyranyl ether with 2-diethylaminoethyl chloride to form 17#-(2-diethylaminoethoxy) - androstan - 3# - ol 3 - tetrahydropyranyl ether, hydrolysing this to the free 3#-ol and esterifying this. 3α-Chloro-17#-(2-diethylaminoethoxy)-androstane is prepared from the corresponding 3#-ol tosylate and KCl. 17#-(2-diethylaminoethoxy) - androstan - 3α - ol is obtained as a by-product in the preparation of 17#-(2- diethylamino ethoxy)-2-androstane from 17#- (2 - diethylaminoethoxy) - androstan - 3# - ol mesylate; similarly 17#-(2-diethylaminoethoxy)- androstan-3α and 3#-ols are obtained from the benzenesulphonate of the 3#-ol. The novel steroids are stated to possess antihypercholesterolaemic, estrogenic, anti-estrogenic, contraceptive, fungicidal and bacteriocidal properties and they may be made up into pharmaceutical compositions with suitable carriers.